An improved survival model of hypoxia/ischaemia in the piglet suitable forneuroprotection studies

The purpose of this study, was to develop a newborn piglet model of hypoxia /ischaemia which would better emulate the clinical situation in the asphyxi ated human neonate and produce a consistent degree of histopathological inj ury following the insult. One-day-old piglets (n = 18) were anaesthetised w ith a mixture of propofol (10 mg/kg/h) and alfentinal (5,5.5 mug/kg/h) i.v. The piglets were intubated and ventilated. Physiological variables were mo nitored continuously. Hypoxia was induced by decreasing the inspired oxygen (FiO(2)) to 3-4% and adjusting FiO(2) to maintain the cerebral function mo nitor peak amplitude at less than or equal to5 muV. The duration of the mil d insult was 20, min while the severe insult was 30 min which included 10 m in where the blood pressure was allowed to fall below 70% of baseline. Cont rol piglets (n=4 of 18) were subjected to the same protocol except for the hypoxic/ischaemic insult. The piglets were allowed to recover from anaesthe sia then euthanased 72 It after the insult. The brains were perfusion-fixed , removed and embedded in paraffin. Coronal sections were stained by haemat oxylin/eosin. A blinded observer examined the frontal and parietal cortex, hippocampus, basal ganglia, thalamus and cerebellum for the degree of damag e. The total mean histology score for the five areas of the brain for the s evere insult was 15.6 +/-4.4 (mean +/-S.D., n=7), whereas no damage was see n in either the mild insult (n=4) or control groups. This 'severe damage' m odel produces a consistent level of damage and will prove useful for examin ing potential neuroprotective therapies in the neonatal brain. (C) 2001 Els evier Science BY. All rights reserved.